Gene‐ and pathway‐level analyses of iCOGS variants highlight novel signaling pathways underlying familial breast cancer susceptibility - Institut Paoli-Calmettes Accéder directement au contenu
Article Dans Une Revue International Journal of Cancer Année : 2021

Gene‐ and pathway‐level analyses of iCOGS variants highlight novel signaling pathways underlying familial breast cancer susceptibility

1 Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe
2 Mines Paris - PSL (École nationale supérieure des mines de Paris)
3 PSL - Université Paris sciences et lettres
4 CESP - Centre de recherche en épidémiologie et santé des populations
5 Centre Léon Bérard [Lyon]
6 CHU Nîmes - Hôpital Universitaire Carémeau [Nîmes]
7 Institut Bergonié [Bordeaux]
8 CHU - BREST - Hôpital Morvan - CHRU de Brest
9 HCL - Hospices Civils de Lyon
10 GHE - Groupement Hospitalier Lyon-Est
11 CHU Rouen
12 Hôpital pasteur [Colmar]
13 Institut Claudius Regaud
14 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
15 Hôpital Bretonneau
16 Institut Sainte Catherine [Avignon]
17 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
18 hôpital couple-enfant [CHU Grenoble Alpes]
19 Clinique de Génétique médicale Guy Fontaine [CHRU LIlle]
20 LBBE - Laboratoire de Biométrie et Biologie Evolutive - UMR 5558
21 Hôpital Dupuytren [CHU Limoges]
22 IMoST - Imagerie Moléculaire et Stratégies Théranostiques
23 UNICANCER/CJP - Centre Jean Perrin [Clermont-Ferrand]
24 Hôpital Arnaud de Villeneuve [CHRU Montpellier]
25 IRCM - U1194 Inserm - UM - Institut de Recherche en Cancérologie de Montpellier
26 HUS - Les Hôpitaux Universitaires de Strasbourg
27 UNICANCER/ICL - Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy]
28 SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD - Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale
29 IPC - Institut Paoli-Calmettes
30 UNICANCER/CRLC - Centre Régional de Lutte contre le Cancer François Baclesse [Caen]
31 UNICANCER/ICO - Institut de Cancérologie de l'Ouest [Angers/Nantes]
32 CH Georges Renon Niort - Centre Hospitalier Georges Renon [Niort]
33 CCS - Centre Catherine-de-Sienne [Nantes]
34 CHU Dijon
35 UNICANCER/CRLCC-CGFL - Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon]
36 institut GIMI - Institut de médecine génomique et d’immunothérapie (Genomic and Immunotherapy Medical Institute)
37 Institut Curie [Paris]
38 IGR - Institut Gustave Roussy
39 CRNL - Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center
40 U830 - Unité de génétique et biologie des cancers
Thierry Frebourg
  • Fonction : Auteur

Résumé

Single-nucleotide polymorphisms (SNPs) in over 180 loci have been associated with breast cancer (BC) through genome-wide association studies involving mostly unselected population-based case-control series. Some of them modify BC risk of women carrying a BRCA1 or BRCA2 (BRCA1/2) mutation and may also explain BC risk variability in BC-prone families with no BRCA1/2 mutation. Here, we assessed the contribution of SNPs of the iCOGS array in GENESIS consisting of BC cases with no BRCA1/2 mutation and a sister with BC, and population controls. Genotyping data were available for 1281 index cases, 731 sisters with BC, 457 unaffected sisters and 1272 controls. In addition to the standard SNP-level analysis using index cases and controls, we performed pedigree-based association tests to capture transmission information in the sibships. We also performed gene- and pathway-level analyses to maximize the power to detect associations with lower-frequency SNPs or those with modest effect sizes. While SNP-level analyses identified 18 loci, gene-level analyses identified 112 genes. Furthermore, 31 Kyoto Encyclopedia of Genes and Genomes and 7 Atlas of Cancer Signaling Network pathways were highlighted (false discovery rate of 5%). Using results from the “index case-control” analysis, we built pathway-derived polygenic risk scores (PRS) and assessed their performance in the population-based CECILE study and in a data set composed of GENESIS-affected sisters and CECILE controls. Although these PRS had poor predictive value in the general population, they performed better than a PRS built using our SNP-level findings, and we found that the joint effect of family history and PRS needs to be considered in risk prediction models.
Fichier principal
Vignette du fichier
ijc.33457.pdf (1.7 Mo) Télécharger le fichier
Origine : Publication financée par une institution

Dates et versions

hal-03345363 , version 1 (17-09-2021)

Licence

Paternité - Pas d'utilisation commerciale - Pas de modification

Identifiants

Citer

Christine Lonjou, Séverine Eon‐marchais, Thérèse Truong, Marie‐gabrielle Dondon, Mojgan Karimi, et al.. Gene‐ and pathway‐level analyses of iCOGS variants highlight novel signaling pathways underlying familial breast cancer susceptibility. International Journal of Cancer, 2021, 148 (8), pp.1895-1909. ⟨10.1002/ijc.33457⟩. ⟨hal-03345363⟩
176 Consultations
64 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More